Phosphatidylinositol (Ptdlns) transfer protein (PITP) is a ubiquitous and abundant cytosolic protein that was discovered some 25 years ago because it can exchange Ptdlns and phosphatidylcholine (PtdCho) between lipid bilayers (for review see Wirtz, 1991). This in vitro activity suggested an in vivo function of PITP in transport of these phospholipids from the site of their synthesis in the endoplasmic reticulum (ER) and the Golgi to other cell membranes. While the phospholipid exchange activity remains the simplest way of assaying PITP, it now appears that the cellular functions of PITP may have little to do with phospholipid transfer per se. Recent studies have indicated that PITP is an essential component of the polyphosphoinositide synthesis machinery and that as such it is required for proper signaling by epidermal growth factor (EGF) and f-Met-Leu-Phe (Thomas et al., 1993; Kauffmann-Zeh et al., 1995) as well as for exocytosis (Hay et al., 1995). These results raise the possibility that the role played by PITP in polyphosphoinositide synthesis may also explain its involvement in intracellular vesicular traffic.